MULTI-ANCESTRY GWAS OF GENERALIZED ANXIETY DISORDER IN THE MILLION VETERAN PROGRAM

Generalized anxiety disorder (GAD) remains underpowered in genetic studies relative to other psychiatric traits. We conducted a multi-ancestry genome-wide association study (GWAS) of GAD in the Million Veteran Program (MVP), including 42,130 cases and 580,993 controls across European (EUR), African (AFR), and admixed American (AMR) ancestry groups. SNP-based heritability was approximately 5% in both EUR and AFR cohorts, indicating comparable and detectable polygenic signal across ancestries. In EUR participants (30,371 cases; 414,334 controls), we identified two genome-wide significant loci, including signals in ESYT3 and near LRRIQ3, along with six additional loci at suggestive significance (P < 1 × 10-6). No genome-wide significant loci were identified in AFR or AMR analyses, consistent with reduced power in currently available non-European samples and underscoring the need for future efforts to prioritize recruitment and inclusion of underrepresented ancestry populations through ongoing large-scale collaborative initiatives. These findings demonstrate detectable polygenic liability for GAD across multiple ancestry groups, alongside differences in locus discovery that likely reflect variation in sample size and power. Increasing non-European representation will be critical for improving gene discovery, fine-mapping resolution, and generalizability of genetic findings for GAD.